Hybrid Additive Microfabrication Scaffold Incorporated with Highly Aligned Nanofibers for Musculoskeletal Tissues

Background:: Latest tissue engineering strategies for musculoskeletal tissues regeneration focus on creating a biomimetic microenvironment closely resembling the natural topology of extracellular matrix. This paper presents a novel musculoskeletal tissue scaffold fabricated by hybrid additive manufacturing method. Methods:: The skeleton of the scaffold was 3D printed by fused deposition modeling, and a layer of random or aligned polycaprolactone nanofibers were embedded between two frames. A parametric study was performed to investigate the effects of process parameters on nanofiber morphology. A compression test was performed to study the mechanical properties of the scaffold. Human fibroblast cells were cultured in the scaffold for 7 days to evaluate the effect of scaffold microstructure on cell growth. Results:: The tip-to-collector distance showed a positive correlation with the fiber alignment, and the electrospinning time showed a negative correlation with the fiber density. With reinforced nanofibers, the hybrid scaffold demonstrated superior compression strength compared to conventional 3D-printed scaffold. The hybrid scaffold with aligned nanofibers led to higher cell attachment and proliferation rates, and a directional cell organization. In addition, there was a nonlinear relationship between the fiber diameter/density and the cell actinfilament density. Conclusion:: This hybrid biofabrication process can be established as a highly efficient and scalable platform to fabricate biomimetic scaffolds with patterned fibrous microstructure, and will facilitate future development of clinical solutions for musculoskeletal tissue regeneration.